新的可行的肝细胞癌的研究设计：一个TSU-68(一种口服的血管生成抑制剂) I/II 临床研究
New feasibility study design with hepatocellular carcinoma: A phase I/II study of TSU-68, an oral angiogenesis inhibitor. Meeting: 2006 ASCO Annual Meeting
Abstract No: 4145
Citation: Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 4145
Author(s): F. Kanai, H. Yoshida, T. Teratani, S. Sato, R. Tateishi, S. Obi, M. Yamashita, T. Kawabe, S. Shiina, M. Omata
Abstract: Background: Hepatocellular carcinoma (HCC) is a devastating disease with limited treatment options at advanced stages. HCC is a highly vascular tumor in which angiogenesis contributes to its pathogenesis. TSU-68 is an oral anti-angiogenesis compound that blocks VEGFR-2, PDGFR, and FGFR. Methods: This is an open-label phase I/II study to characterize the safety, tolerability, pharmacokinetic (PK) profile and efficacy of TSU-68 at 800mg/po daily in adults with unresectable HCC. Patients (Pts) previously treated with surgery, radiofrequency ablation, transcatheter arterial embolization, chemotherapy, or radiotherapy were eligible. Pts were stratified into three groups based on hepatic function: level 1 (no cirrhosis), level 2 (Childs-Pugh A) or level 3 (Childs-Pugh B). The safety, tolerability and PK of TSU-68 were assessed sequentially from level 1 by enrolling 3 pts in each level. The response was evaluated based on RECIST. Results: 15 pts were enrolled: median age = 67 years (range 53-74 years), male/female = 11/4, cirrhosis/no cirrhosis = 12/3, HCV/HBV/alcohol = 12/2/1. 2 pts at level 3 who received 800 mg/d experienced DLTs (CTC grade 3 abdominal pain and ascites). The dose was reduced to 400 mg/d in an additional 3 pts at level 3 (no DLT observed). The most common adverse events were: hypoalbuminemia, diarrhea, abdominal pain, fever, and AST/ALT elevation. PK data from 12 pts (3 at level 1; 3 at level 2; 6 at level 3) indicated that the area under the curve (AUC) of TSU-68 was similar from level 1 to 3, and biologically active levels of TSU-68 could be reached at a dose of 400 mg/d. One pt had a partial response, 7 pts had stable disease (2 pts for over 12 months) and 7 pts had progressive disease. Tumor necrosis was observed in 8 pts. Conclusions: The study design based on hepatic function is useful to assess the safety of anti-tumor agent in pts with impaired liver function. A dose of 400 mg/d TSU-68 is well tolerated in pts with HCC. While the study is still on going, the preliminary results suggest that TSU-68 has anti-tumor activity against HCC. http://www.pancas.com/yeNewsInfo.asp?id=77 http://www.taiho.co.jp/recruit/question/question5.html | 
发表于 2007-1-28 06:23
